Recently, medium-dose UVA1 phototherapy (50 J/cm2) has achieved great therapeutic success within the treatment of severe atopic dermatitis (AD). Histologically, AD is recognised by a pathological perivascular dermal infiltrate including T lymphocytes, eosinophils and Langerhans cells. The purpose of our study was to investigate the extent to which UVA1 irradiation is able to modulate the mononuclear dermal inflammatory infiltrate using different monoclonal antibodies. Biopsy specimens before and after treatment with medium-dose UVA1 irradiation (cumulative dose: 750 J/cm2) from 15 patients suffering from severe AD were analysed immunohistochemically concerning the presence of CD4+ and CD8+ T lymphocytes, CD1a+ Langerhans cells and EG2+ activated eosinophils. Compared to lesional skin of patients with AD before UVA1 irradiation, the relative number of CD4+ cells, CD1a+ dendritic cells and activated EG2+ eosinophils within the dermal infiltrate could be decreased significantly after treatment. In contrast, medium-dose UVA1 phototherapy led to a significant increase of the percentage of dermal CD8+ cells. These alterations were closely linked to a decrease of the absolute skin-infiltrating cells and a substantial clinical improvement of the skin. In summary, our findings demonstrate that medium-dose UVA1 irradiation leads to a remarkable modulation of the dermal mononuclear infiltrate in patients with severe atopic dermatitis referring to a decrease of dermal Langerhans cells, activated eosinophils and CD4 cell count as well as to a relative increase of CD8+ lymphocytes. The immunomodulation of the cutaneous infiltrate is associated with a depletion of cytotoxic agents, the defective IgE overproduction and the aberrant presence of T lymphocytes combined with the pathological cytokine pattern.